I. Antihypertensive agents, like clonidine, propranolol and gamma-methyldopa, have been reported to produce their effects, at least in part, by acting on the CNS. (a) To determine the relative potency of this CNS action as compared to the possible peripheral effect. The drugs will be administered into the vertebral artery, and after recovery, intravenously to ascertain their effects on the central nervous system. These studies will provide some information regarding the potency ratio to evaluate the relative importance of their central action. (b) Effects on the spontaneous firing rate of vasomotor neurons. The vasomotor neurons can be identified by elevating or lowering the blood pressure by i.v. injections of minute amounts of norepinephrine or acetylcholine, respectively. Thus, the spontaneous firing rate of these neurons is significantly reduced following a slight increase in the arterial pressure, and vice versa. Once the neurons are identified, the effects of drugs administered via the microiontophoretic technique will be observed on the spontaneous firing rate of these neurons to determine if the agents have any inhibitory action. To serve as controls, these agents will also be studied on other indifferent neurons. II. Locus of antimetic action of penfluridol. Penfluridol is a new, potent and orally effective, long-acting neurleptic agent. When it was given orally 0.01 mg/kg, it prevented apomorphine, 0.01-0.015 mg/kg i.v., (threshold dose) induced emesis for six weeks. Penfluridol does not prevent dogs from vomiting to other emetic agents, such as ouabain, 0.06 mg/kg i.v. Thus, it is concluded that penfluridol acts at CTZ. The problem is to find out why its antiemetic action lasts for such a long time. BIBLIOGRAPHIC REFERENCES: Lee, H.K. and S.C. Wang. Mechanism of morphine-induced miosis in the dog. J. Pharmacol. Exp. Ther. 192: 415-431, 1975. Hirsh, K. and S.C. Wang. Respiratory stimulant effects of ethamivan and picrotoxin. J. Pharmacol. Exp. Ther. 193: 657-663, 1975.